Research Project

研究项目

• 批准号: 10765810
• 负责人: Daniel J Clauw
• 金额: $ 47.93万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-26 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10765810
• 关键词: Research; Project

PROJECT SUMMARY / ABSTRACT RESEARCH PROJECT The evidence-based treatments for cLBP typically include a combination of pharmacologic, non-pharmacologic and procedural treatments. However, none of these treatments works well in more than a fraction of patients, and at present there is little guidance regarding what treatment should be used in which patients (i.e. precision medicine). The BACPAC precision medicine initiative for cLBP will attempt to solve this problem by deeply phenotyping cLBP participants to identify the various underlying mechanisms causing cLBP. We feel that a critical element of such phenotyping is to also understand which participants respond to which therapies, so that we can then eventually choose the appropriate treatment for a cLBP patient based on which underlying mechanisms are contributing to their pain and dysfunction. Our central hypothesis in our BACPAC MRC Research Project is that an Interventional Response Phenotyping study can identify individuals with different underlying mechanisms for their pain who thus respond differentially to evidence-based interventions for cLBP”. To address this hypothesis, we will conduct a randomized controlled SMART study of cLBP with the following three aims. The first aim is to perform an Interventional Response Phenotyping study in a cohort of cLBP patients. We will perform a pragmatic trial using a cohort of cLBP patients (n=500), who will receive a sequence of interventions known to be effective in cLBP. For 6 weeks, all cLBP participants will receive a web- based self-management program for pain. After six weeks, individuals who remain symptomatic will be enrolled in a Sequential, Multiple Assessment, Randomized Trial (SMART) design study and randomized to a series of treatments, including: a) mindfulness based cognitive therapy, b) physical therapy/exercise, c) acupressure, d) duloxetine, or e) pregabalin. After 12 weeks, individuals who remain symptomatic will be re-randomized to a different treatment for an additional 12 weeks. Having this information on all participants, we will overlay Aims 2 and 3, which will identify the subsets of participants that respond to each treatment. In Aim 2, we will show that currently available, clinically-derived measures, can predict differential responsiveness to the above therapies. In Aim 3, a subset of the individuals in Aims 1 and 2 will receive deeper phenotyping (n=200), to identify new experimental measures that predict differential responsiveness to each of the above therapies, as well as to infer mechanisms of action of treatments. These deep phenotyping visits take nearly an entire day each, will be performed prior to each treatment period and at the completion of the study, and will include functional neuroimaging, quantitative sensory testing, plasma measures of inflammation, and measures of autonomic tone.

项目概要/摘要 研究项目 cLBP 的循证治疗通常包括药物、非药物治疗的组合 然而，这些治疗方法对一小部分患者都没有效果， 目前，对于哪些患者应采用何种治疗（即精准治疗）几乎没有指导。 针对 cLBP 的 BACPAC 精准医学计划将尝试通过深入解决这一问题。 对 cLBP 参与者进行表型分析，以确定导致 cLBP 的各种潜在机制。 这种表型分析的关键要素还在于了解哪些参与者对哪些疗法有反应，因此 然后我们最终可以根据潜在的情况为 cLBP 患者选择合适的治疗方法 我们在 BACPAC MRC 中的核心假设是导致他们的疼痛和功能障碍的机制。 研究项目是介入反应表型研究可以识别具有不同症状的个体 因此，他们对基于证据的干预措施的反应不同 为了解决这一假设，我们将进行一项关于 cLBP 的随机对照 SMART 研究 以下三个目标第一个目标是在一组人群中进行干预反应表型研究。 我们将使用一组 cLBP 患者（n=500）进行一项实用试验，这些患者将接受 已知对 cLBP 有效的干预措施序列 在 6 周内，所有 cLBP 参与者都将收到网络- 六周后，仍存在症状的个体将被纳入基于疼痛的自我管理计划。 在一项序贯、多重评估、随机试验 (SMART) 设计研究中，并随机分配到一系列 治疗，包括：a) 基于正念的认知治疗，b) 物理治疗/运动，c) 指压按摩，d) 度洛西汀，或 e) 普瑞巴林 12 周后，仍然有症状的个体将被重新随机分配至另一组。 获得所有参与者的这些信息后，再进行 12 周的不同治疗，我们将覆盖目标。 2 和 3，这将确定对每种治疗有反应的参与者子集，我们将在目标 2 中展示。 目前可用的、临床衍生的测量方法可以预测对上述情况的不同反应 在目标 3 中，目标 1 和 2 中的一部分个体将接受更深入的表型分析 (n=200)，以 确定新的实验措施来预测对上述每种疗法的不同反应，如 以及推断治疗的作用机制，这些深入的表型分析访问需要几乎一整天的时间。 每一项都将在每个治疗期之前和研究完成时进行，并将包括 功能性神经影像、定量感觉测试、炎症的血浆测量以及 自主语气。